5,991 research outputs found
Plasma Brain Dynamics (PBD): II. Quantum Effects on Consciousness
This article studies the quantum effect of the brain neuronal system on both normal and abnormal conscious states. It develops Plasma Brain Dynamics (PBD) to obtain a set of kinetic quantum-plasma Wigner-Poisson equations. The model is established under typical electrostatic and collision-free conditions in both the absence and presence of an external magnetic field. The quantum perturbation is solved analytically by employing a backward-mapping approach to the motion of electrons. Results expose that the quantum perturbation turns out to be zero at normal conscious states; but no more than 11% of the classical perturbation under assumed abnormal situations like a sudden head trauma, mood disorder, etc. The introduction of the magnetic field does not influence the results
Structure and dynamics of the E. coli chemotaxis core signaling complex by cryo-electron tomography and molecular simulations
To enable the processing of chemical gradients, chemotactic bacteria possess large arrays of transmembrane chemoreceptors, the histidine kinase CheA, and the adaptor protein CheW, organized as coupled core-signaling units (CSU). Despite decades of study, important questions surrounding the molecular mechanisms of sensory signal transduction remain unresolved, owing especially to the lack of a high-resolution CSU structure. Here, we use cryo-electron tomography and sub-tomogram averaging to determine a structure of the Escherichia coli CSU at sub-nanometer resolution. Based on our experimental data, we use molecular simulations to construct an atomistic model of the CSU, enabling a detailed characterization of CheA conformational dynamics in its native structural context. We identify multiple, distinct conformations of the critical P4 domain as well as asymmetries in the localization of the P3 bundle, offering several novel insights into the CheA signaling mechanism
National Trends in Statin Use by Coronary Heart Disease Risk Category
BACKGROUND: Only limited research tracks United States trends in the use of statins recorded during outpatient visits, particularly use by patients at moderate to high cardiovascular risk. METHODS AND FINDINGS: Data collected between 1992 and 2002 in two federally administered surveys provided national estimates of statin use among ambulatory patients, stratified by coronary heart disease risk based on risk factor counting and clinical diagnoses. Statin use grew from 47% of all lipid-lowering medications in 1992 to 87% in 2002, with atorvastatin being the leading medication in 2002. Statin use by patients with hyperlipidemia, as recorded by the number of patient visits, increased significantly from 9% of patient visits in 1992 to 49% in 2000 but then declined to 36% in 2002. Absolute increases in the rate of statin use were greatest for high-risk patients, from 4% of patient visits in 1992 to 19% in 2002. Use among moderate-risk patients increased from 2% of patient visits in 1992 to 14% in 1999 but showed no continued growth subsequently. In 2002, 1 y after the release of the Adult Treatment Panel III recommendations, treatment gaps in statin use were detected for more than 50% of outpatient visits by moderate- and high-risk patients with reported hyperlipidemia. Lower statin use was independently associated with younger patient age, female gender, African American race (versus non-Hispanic white), and non-cardiologist care. CONCLUSION: Despite notable improvements in the past decade, clinical practice fails to institute recommended statin therapy during many ambulatory visits of patients at moderate-to-high cardiovascular risk. Innovative approaches are needed to promote appropriate, more aggressive statin use for eligible patients
Noiseless nonreciprocity in a parametric active device
Nonreciprocal devices such as circulators and isolators belong to an
important class of microwave components employed in applications like the
measurement of mesoscopic circuits at cryogenic temperatures. The measurement
protocols usually involve an amplification chain which relies on circulators to
separate input and output channels and to suppress backaction from different
stages on the sample under test. In these devices the usual reciprocal symmetry
of circuits is broken by the phenomenon of Faraday rotation based on magnetic
materials and fields. However, magnets are averse to on-chip integration, and
magnetic fields are deleterious to delicate superconducting devices. Here we
present a new proposal combining two stages of parametric modulation emulating
the action of a circulator. It is devoid of magnetic components and suitable
for on-chip integration. As the design is free of any dissipative elements and
based on reversible operation, the device operates noiselessly, giving it an
important advantage over other nonreciprocal active devices for quantum
information processing applications.Comment: 17 pages, 4 figures + 12 pages Supplementary Informatio
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Peptidomic discovery of short open reading frame-encoded peptides in human cells
The amount of the transcriptome that is translated into polypeptides is of fundamental importance. We developed a peptidomic strategy to detect short ORF (sORF)-encoded polypeptides (SEPs) in human cells. We identified 90 SEPs, 86 of which are novel, the largest number of human SEPs ever reported. SEP abundances range from 10-1000 molecules per cell, identical to known proteins. SEPs arise from sORFs in non-coding RNAs as well as multi-cistronic mRNAs, and many SEPs initiate with non-AUG start codons, indicating that non-canonical translation may be more widespread in mammals than previously thought. In addition, coding sORFs are present in a small fraction (8/1866) of long intergenic non-coding RNAs (lincRNAs). Together, these results provide the strongest evidence to date that the human proteome is more complex than previously appreciated
Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice
Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+) and IgA(+) antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge
The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy ± chemotherapy
BACKGROUND: Several parameters of the tumor microenvironment, such as hypoxia, inflammation and angiogenesis, play a critical role in tumor aggressiveness and treatment response. A major question remains if these markers can be used to stratify patients to certain treatment protocols. The purpose of this study was to investigate the inter-relationship and the prognostic significance of several biological and clinicopathological parameters in patients with head and neck squamous cell carcinoma (HNSCC) treated by radiotherapy ± chemotherapy. METHODS: We used two subgroups of a retrospective series for which CT-determined tumoral perfusion correlated with local control. In the first subgroup (n = 67), immunohistochemistry for carbonic anhydrase IX (CA IX) and glucose transporter-1 (GLUT-1) was performed on the pretreatment tumor biopsy. In the second subgroup (n = 34), enzyme linked immunosorbent assay (ELISA) was used to determine pretreatment levels of the cytokines vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in serum. Correlation was investigated between tumoral perfusion and each of these biological markers, as well as between the markers mutually. The prognostic value of these microenvironmental parameters was also evaluated. RESULTS: For CA IX and GLUT-1, the combined assessment of patients with both markers expressed above the median showed an independent correlation with local control (p = 0.02) and disease-free survival (p = 0.04) with a trend for regional control (p = 0.06). In the second subgroup, IL-6 pretreatment serum level above the median was the only independent predictor of local control (p = 0.009), disease-free survival (p = 0.02) and overall survival (p = 0.005). CONCLUSION: To our knowledge, we are the first to report a link in HNSCC between IL-6 pretreatment serum levels and radioresistance in vivo. This link is supported by the strong prognostic association of pretreatment IL-6 with local control, known to be the most important parameter to judge radiotherapy responses. Furthermore, the combined assessment of CA IX and GLUT-1 correlated independently with prognosis. This is a valuable indication that a combined approach is important in the investigation of prognostic markers
Theory of interlayer tunneling in bi-layer quantum Hall ferromagnets
Spielman et al. have recently observed a large zero-bias peak in the tunnel
conductance of a bi-layer system in a quantum Hall ferromagnet state. We argue
that disorder-induced topological defects in the pseudospin order parameter
limit the peak size and destroy the predicted Josephson effect. We predict that
the peak would be split and shifted by an in-plane magnetic field in a way that
maps the dispersion relation of the ferromagnet's Goldstone mode. We also
predict resonant structures in the DC I-V characteristic under bias by an {\em
ac} electric field.Comment: 4 pages, no figures, submitted to Physical Review Letter
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